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1.
ACS Appl Mater Interfaces ; 16(4): 4333-4347, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38240200

RESUMO

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide, among which 80% is basal cell carcinoma (BCC). Current therapies' low efficacy, side effects, and high recurrence highlight the need for alternative treatments. In this work, a partially reduced nanographene oxide (p-rGOn) developed in our laboratory was used. It has been achieved through a controlled reduction of nanographene oxide via UV-C irradiation that yields small nanometric particles (below 200 nm) that preserve the original water stability while acquiring high light-to-heat conversion efficiency. The latter is explained by a loss of carbon-oxygen single bonds (C-O) and the re-establishment of sp2 carbon bonds. p-rGOn was incorporated into a Carbopol hydrogel together with the anticancer drug 5-fluorouracil (5-FU) to evaluate a possible combined PTT and chemotherapeutic effect. Carbopol/p-rGOn/5-FU hydrogels were considered noncytotoxic toward normal skin cells (HFF-1). However, when A-431 skin cancer cells were exposed to NIR irradiation for 30 min in the presence of Carbopol/p-rGOn/5-FU hydrogels, almost complete eradication was achieved after 72 h, with a 90% reduction in cell number and 80% cell death of the remaining cells after a single treatment. NIR irradiation was performed with a light-emitting diode (LED) system, developed in our laboratory, which allows adjustment of applied light doses to achieve a safe and selective treatment, instead of the standard laser systems that are associated with damages in the healthy tissues in the tumor surroundings. Those are the first graphene-based materials containing pharmaceutical formulations developed for BCC phototherapy.


Assuntos
Grafite , Fotoquimioterapia , Neoplasias Cutâneas , Humanos , Grafite/química , Fluoruracila/farmacologia , Composição de Medicamentos , Linhagem Celular Tumoral , Fototerapia , Neoplasias Cutâneas/tratamento farmacológico , Carbono , Óxidos , Hidrogéis/farmacologia , Hidrogéis/química
2.
Acta Biomater ; 173: 351-364, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984630

RESUMO

Developing biocompatible, non-fouling and biodegradable hydrogels for blood-contacting devices remains a demanding challenge. Such materials should promote natural healing, prevent clotting, and undergo controlled degradation. This study evaluates the biocompatibility and biodegradation of degradable poly(2-hydroxyethyl methacrylate) (d-pHEMA) hydrogels with or without reinforcement with oxidized few-layer graphene (d-pHEMA/M5ox) in a long term implantation in rats, assessing non-desired side-effects (irritation, chronic toxicity, immune response). Subcutaneous implantation over 6 months revealed degradation of both hydrogels, despite slower for d-pHEMA/M5ox, with degradation products found in intracellular vesicles. No inflammation nor infection at implantation areas were observed, and no histopathological findings were detected in parenchymal organs. Immunohistochemistry confirmed d-pHEMA and d-pHEMA/M5ox highly anti-adhesiveness. Gene expression of macrophages markers revealed presence of both M1 and M2 macrophages at all timepoints. M1/M2 profile after 6 months reveals an anti-inflammatory environment, suggesting no chronic inflammation, as also demonstrated by cytokines (IL-α, TNF-α and IL-10) analysis. Overall, modification of pHEMA towards a degradable material was successfully achieved without evoking a loss of its inherent properties, specially its anti-adhesiveness and biocompatibility. Therefore, these hydrogels hold potential as blank-slate for further modifications that promote cellular adhesion/proliferation for tissue engineering applications, namely for designing blood contacting devices with different load bearing requirements. STATEMENT OF SIGNIFICANCE: Biocompatibility, tunable biodegradation kinetics, and suitable immune response with lack of chronic toxicity and irritation, are key features in degradable blood contact devices that demand long-term exposure. We herein evaluate the 6-month in vivo performance of a degradable and hemocompatible anti-adhesive hydrogel based in pHEMA, and its mechanically reinforced formulation with few-layer graphene oxide. This subcutaneous implantation in a rat model, shows gradual degradation with progressive changes in material morphology, and no evidence of local inflammation in surrounding tissue, neither signs of inflammation or adverse reactions in systemic organs, suggesting biocompatibility of degradation products. Such hydrogels exhibit great potential as a blank slate for tissue engineering applications, including for blood contact, where cues for specific cells can be incorporated.


Assuntos
Grafite , Ratos , Animais , Grafite/farmacologia , Poli-Hidroxietil Metacrilato/química , Hidrogéis/farmacologia , Hidrogéis/química , Engenharia Tecidual , Inflamação , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química
4.
ACS Biomater Sci Eng ; 9(6): 3712-3722, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37256830

RESUMO

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.


Assuntos
Eletrônica Médica , Hidrogéis , Elétrons , Poli-Hidroxietil Metacrilato
5.
Acta Biomater ; 164: 253-268, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37121371

RESUMO

Degradable biomaterials for blood-contacting devices (BCDs) are associated with weak mechanical properties, high molecular weight of the degradation products and poor hemocompatibility. Herein, the inert and biocompatible FDA approved poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel was turned into a degradable material by incorporation of different amounts of a hydrolytically labile crosslinking agent, pentaerythritol tetrakis(3-mercaptopropionate). In situ addition of 1wt.% of oxidized graphene-based materials (GBMs) with different lateral sizes/thicknesses (single-layer graphene oxide and oxidized forms of few-layer graphene materials) was performed to enhance the mechanical properties of hydrogels. An ultimate tensile strength increasing up to 0.2 MPa (293% higher than degradable pHEMA) was obtained using oxidized few-layer graphene with 5 µm lateral size. Moreover, the incorporation of GBMs has demonstrated to simultaneously tune the degradation time, which ranged from 2 to 4 months. Notably, these features were achieved keeping not only the intrinsic properties of inert pHEMA regarding water uptake, wettability and cytocompatibility (short and long term), but also the non-fouling behavior towards human cells, platelets and bacteria. This new pHEMA hydrogel with degradation and biomechanical performance tuned by GBMs, can therefore be envisioned for different applications in tissue engineering, particularly for BCDs where non-fouling character is essential. STATEMENT OF SIGNIFICANCE: Suitable mechanical properties, low molecular weight of the degradation products and hemocompatibility are key features in degradable blood contacting devices (BCDs), and pave the way for significant improvement in the field. In here, a hydrogel with outstanding anti-adhesiveness (pHEMA) provides hemocompatibility, the presence of a degradable crosslinker provides degradability, and incorporation of graphene oxide reestablishes its strength, allowing tuning of both degradation and mechanical properties. Notably, these hydrogels simultaneously provide suitable water uptake, wettability, cytocompatibility (short and long term), no acute inflammatory response, and non-fouling behavior towards endothelial cells, platelets and bacteria. Such results highlight the potential of these hydrogels to be envisioned for applications in tissue engineered BCDs, namely as small diameter vascular grafts.


Assuntos
Grafite , Hidrogéis , Humanos , Hidrogéis/farmacologia , Poli-Hidroxietil Metacrilato , Grafite/farmacologia , Células Endoteliais , Materiais Biocompatíveis/farmacologia , Água
6.
Cureus ; 15(1): e33599, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36788831

RESUMO

Biliary ascariasis is rare in non-endemic areas. This infection is associated with severe complications of the biliary tract, which can become a medical emergency. Treatment with oral anthelmintics is often effective, but, in some cases, surgery is required.  We describe an unusual case of ultrasound diagnosis of biliary ascariasis in the gallbladder in a patient who, besides residing in a low-prevalence area of the infection, did not present with biliary tract manifestations. We intend to raise awareness of this clinical entity in non-endemic areas, where this diagnosis is not usually considered. A brief review of the subject is also presented.

7.
Cureus ; 14(11): e31787, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36579262

RESUMO

Mycobacterium marinum is a non-tuberculous mycobacteria present in natural and non-chlorinated bodies of water. It is a known fish pathogen but can also cause human disease. It usually causes cutaneous lesions but in rare cases may originate more invasive diseases with the involvement of deep structures. We describe three cases of patients with cutaneous infection by M. marinum evaluated in a tertiary care center, two with confirmed infection and one with a presumptive diagnosis based on clinical and epidemiological features. A brief bibliographic review of M. marinum infections is then presented to support the theme. We aim to alert one to the difficulties in establishing the correct diagnosis of this infection, emphasize the importance of a high degree of suspicion for its identification, and review the therapeutic management options.

8.
Int J Mol Sci ; 23(4)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35216431

RESUMO

Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.


Assuntos
Grafite/química , Hidrogéis/química , Polietilenoglicóis/química , Adesivos/química , Materiais Biocompatíveis/química , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Polímeros/química , Engenharia Tecidual/métodos
9.
Cureus ; 14(12): e32908, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36699756

RESUMO

Recurrent respiratory papillomatosis (RRP) is a rare manifestation of human papillomavirus (HPV) infection. It is characterized by relapsing bulky papillomas in the respiratory tract, which are usually benign in nature. We describe a challenging case of RRP in an HIV-infected patient with extensive pulmonary disease, presenting with worsening dyspnea. The interaction between HPV with HIV as a coinfection is still not completely understood, particularly the role of HIV-associated immunosuppression in RRP. Our main goal is to raise awareness of this clinical entity and to promote further studies on its management, particularly in specific populations such as HIV-infected individuals. A brief review of the theme is also presented.

10.
ACS Appl Mater Interfaces ; 13(28): 32662-32672, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34240610

RESUMO

The lack of small-diameter vascular grafts (inner diameter <5 mm) to substitute autologous grafts in arterial bypass surgeries has a massive impact on the prognosis and progression of cardiovascular diseases, the leading cause of death globally. Decellularized arteries from different sources have been proposed as an alternative, but their poor mechanical performance and high collagen exposure, which promotes platelet and bacteria adhesion, limit their successful application. In this study, these limitations were surpassed for decellularized umbilical cord arteries through the coating of their lumen with graphene oxide (GO). Placental and umbilical cord arteries were decellularized and perfused with a suspension of GO (C/O ratio 2:1) with ∼1.5 µm lateral size. A homogeneous GO coating that completely covered the collagen fibers was obtained for both arteries, with improvement of mechanical properties being achieved for umbilical cord decellularized arteries. GO coating increased the maximum force in 27%, the burst pressure in 29%, the strain in 25%, and the compliance in 10%, compared to umbilical cord decellularized arteries. The achieved theoretical burst pressure (1960 mmHg) and compliance (13.9%/100 mmHg) are similar to the human saphenous vein and mammary artery, respectively, which are used nowadays as the gold standard in coronary and peripheral artery bypass surgeries. Furthermore, and very importantly, coatings with GO did not compromise the endothelial cell adhesion but decreased platelet and bacteria adhesion to decellularized arteries, which will impact on the prevention of thrombosis and infection, until full re-endothetialization is achieved. Overall, our results reveal that GO coating has an effective role in the improvement of decellularized umbilical cord artery performance, which is a huge step toward their application as a small-diameter vascular graft.


Assuntos
Prótese Vascular , Materiais Revestidos Biocompatíveis/química , Grafite/química , Artérias Umbilicais/química , Aderência Bacteriana/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Córion/irrigação sanguínea , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Placenta/irrigação sanguínea , Gravidez
11.
Materials (Basel) ; 14(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070414

RESUMO

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5% of the mass of GOn dispersion (at a concentration of 1000 µg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild the photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, Gon's potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

12.
Mol Microbiol ; 116(3): 890-908, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34184334

RESUMO

The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.


Assuntos
Lisofosfatidilcolinas/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Sequência de Aminoácidos , Animais , Diferenciação Celular , Doença de Chagas/parasitologia , Técnicas de Inativação de Genes/métodos , Interações Hospedeiro-Parasita , Humanos , Lisofosfatidilcolinas/química , Macrófagos , Camundongos , Simulação de Acoplamento Molecular , Filogenia , Fator de Ativação de Plaquetas/química , Conformação Proteica , Proteínas de Protozoários/química , Receptores de Adiponectina/química , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Receptores de Progesterona/química , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Trypanosoma cruzi/química
13.
Biomater Sci ; 9(9): 3362-3377, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949373

RESUMO

Thrombosis and infection are the leading causes of blood-contacting device (BCD) failure, mainly due to the poor performance of existing biomaterials. Poly(2-hydroxyethyl methacrylate) (pHEMA) has excellent hemocompatibility but the weak mechanical properties impair its use as a bulk material for BCD. As such, pHEMA has been explored as a coating, despite the instability and difficulty of attachment to the underlying polymer compromise its success. This work describes the hydrogel composites made of pHEMA and graphene-based materials (GBM) that meet the biological and mechanical requirements for a stand-alone BCD. Five GBM differing in thickness, oxidation degree, and lateral size were incorporated in pHEMA, revealing that only oxidized-GBM can reinforce pHEMA. pHEMA/oxidized-GBM composites are cytocompatible and prevent the adhesion of endothelial cells, blood platelets, and bacteria (S. aureus), thus maintaining pHEMA's anti-adhesive properties. As a proof of concept, the thrombogenicity of the tubular prototypes of the best formulation (pHEMA/Graphene oxide (GO)) was evaluated in vivo, using a porcine arteriovenous-shunt model. pHEMA/GO conduits withstand the blood pressure and exhibit negligible adhesion of blood components, revealing better hemocompatibility than ePTFE, a commercial material for vascular access. Our findings reveal pHEMA/GO, a synthetic and off-the-shelf hydrogel, as a preeminent material for the design of blood-contacting devices that prevent thrombosis and bacterial adhesion.


Assuntos
Grafite , Poli-Hidroxietil Metacrilato , Animais , Materiais Biocompatíveis/farmacologia , Células Endoteliais , Staphylococcus aureus , Suínos
14.
Sci Rep ; 10(1): 19564, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177617

RESUMO

ATP-binding cassette (ABC) type I importers are widespread in bacteria and play a crucial role in its survival and pathogenesis. They share the same modular architecture comprising two intracellular nucleotide-binding domains (NBDs), two transmembrane domains (TMDs) and a substrate-binding protein. The NBDs bind and hydrolyze ATP, thereby generating conformational changes that are coupled to the TMDs and lead to substrate translocation. A group of multitask NBDs that are able to serve as the cellular motor for multiple sugar importers was recently discovered. To understand why some ABC importers share energy-coupling components, we used the MsmX ATPase from Bacillus subtilis as a model for biological and structural studies. Here we report the first examples of functional hybrid interspecies ABC type I importers in which the NBDs could be exchanged. Furthermore, the first crystal structure of an assigned multitask NBD provides a framework to understand the molecular basis of the broader specificity of interaction with the TMDs.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/química , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Adenosina Trifosfatases/genética , Motivos de Aminoácidos , Bacillus subtilis/química , Biologia Computacional/métodos , Cristalografia por Raios X , Firmicutes/química , Firmicutes/metabolismo , Bactérias Gram-Negativas/química , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/química , Bactérias Gram-Positivas/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida , Domínios Proteicos
15.
Zootaxa ; 4820(1): zootaxa.4820.1.11, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-33056089

RESUMO

A new species of Bessierus Thomas Orth, formerly a monotypic genus, is described from Amapá State, Brazil. The type species of the genus, B. doloris Thomas Orth, had only its nymphs described until recently, when its male imago was associated to nymphs mainly based on pigmentation pattern. Bessierus riobranco sp. n. here described has no significant difference on pigmentation pattern from B. doloris, thus the new species could be the male imago of B. doloris, and the putative imago of B. doloris a new species, or even both described imagoes could be new species. Still, a new male imago existence cannot be neglected and we opted to provide a properly description, diagnosis and illustration, hence contributing to the knowledge of mayfly neotropical diversity and future research on the genus. The generic concept of Bessierus and its type species diagnoses are altered to accommodate the new species, and a new record of B. doloris is provided.


Assuntos
Ephemeroptera , Animais , Brasil , Masculino , Ninfa , Pigmentação
16.
Zootaxa ; 4759(1): zootaxa.4759.1.7, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33056935

RESUMO

Three unusual nymphs of Euthyplociidae, subfamily Euthyplociinae, are described from Ecuador. A new genus and new species are established to accommodate these individuals. The morphologically unique specimens are defined by the following characters: short, stout tusks lacking spine-like setae but densely covered with long, hair-like setae; head almost as long as wide; long, quadrate clypeus with acute apicolateral projections; apex of 3rd segment of labial palp acute; apex of 3rd segment of maxillary palp acute and narrow. The hind wing is small, similar to that of Mesoplocia. An ongoing study of the phylogeny of the family recovers Dasyplocia gen. nov. as closely related to Euthyplocia and Mesoplocia.


Assuntos
Ephemeroptera , Animais , Equador , Ninfa , Filogenia , Asas de Animais
17.
Polymers (Basel) ; 12(8)2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32824495

RESUMO

Using a one-step thermal reduction and non-covalent chemical functionalization process, PEGylated reduced nanographene oxide (rGOn-PEG) was produced from nanographene oxide (GOn) and characterized in terms of particle size, dispersion stability, chemistry, and photothermal properties, in view of its use for photothermal therapy (PTT) of non-melanoma skin cancer. GOn infrared spectrum presented more intense bands assigned to oxygen containing functional groups than observed for rGOn-PEG. GOn C/O ratio decreased more than 50% comparing with rGOn-PEG and nitrogen was present in the latter (N at % = 20.6) due to introduction of PEG-NH2. Thermogravimetric analysis allowed estimating the amount of PEG in rGOn-PEG to be of about 56.1%. Simultaneous reduction and PEGylation increased the lateral dimensions from 287 ± 139 nm to 521 ± 397 nm, as observed by transmission electron microscopy and dynamic light scattering. rGOn-PEG exhibited ≈13-fold higher absorbance in the near-infrared radiation (NIR) region, as compared to unmodified GOn. Low power (150 mW cm-2) NIR irradiation using LEDs resulted in rGOn-PEG heating up to 47 °C, which is within the mild PTT temperature range. PEGylation strongly enhanced the dispersibility of rGOn in physiological media (phosphate buffered saline, fetal bovine serum, and cell culture medium) and also improved the biocompatibility of rGOn-PEG, in comparison to GOn (25-250 µg mL-1). After a single NIR LED irradiation treatment of 30 min, a decrease of ≈38% in A-431 cells viability was observed for rGOn-PEG (250 µg mL-1). Together, our results demonstrate the potential of irradiating rGOn-PEG using lower energy, cheaper, smaller, and safer LEDs, as alternative to high power lasers, for NIR mild hyperthermia therapy of cancer, namely non-melanoma skin cancer.

19.
Acta Biomater ; 114: 206-220, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622054

RESUMO

Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.


Assuntos
Quitosana , Infecções por Helicobacter , Helicobacter pylori , Animais , Quitosana/farmacologia , Mucosa Gástrica , Infecções por Helicobacter/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microesferas
20.
Mater Sci Eng C Mater Biol Appl ; 109: 110537, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228892

RESUMO

Implantable medical devices infection and consequent failure is a severe health issue, which can result from bacterial adhesion, growth, and subsequent biofilm formation at the implantation site. Graphene-based materials, namely graphene oxide (GO), have been described as potential antibacterial agents when immobilized and exposed in polymeric matrices. This work focuses on the development of antibacterial and biocompatible 3D fibrous scaffolds incorporating GO. Poly(ε-caprolactone) scaffolds were produced, with and without GO, using wet-spinning combined with additive manufacturing. Scaffolds with different GO loadings were evaluated regarding physical-chemical characterization, namely GO surface exposure, antibacterial properties, and ability to promote human cells adhesion. Antimicrobial properties were evaluated through live/dead assays performed with Gram-positive and Gram-negative bacteria. 2 h and 24 h adhesion assays revealed a time-dependent bactericidal effect in the presence of GO, with death rates of adherent S. epidermidis and E. coli reaching ~80% after 24 h of contact with scaffolds with the highest GO concentration. Human fibroblasts cultured for up to 14 days were able to adhere and spread over the fibers, independently of the presence of GO. Overall, this work demonstrates the potential of GO-containing fibrous scaffolds to be used as biomaterials that hinder bacterial infection, while allowing human cells adhesion.


Assuntos
Anti-Infecciosos , Escherichia coli/crescimento & desenvolvimento , Grafite , Poliésteres , Impressão Tridimensional , Staphylococcus epidermidis/crescimento & desenvolvimento , Alicerces Teciduais/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Grafite/química , Grafite/farmacologia , Humanos , Poliésteres/química , Poliésteres/farmacologia
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